ABSTRACT: Objectives: The objective of this paper is to accomplish a systematic review of the infection hypothesis of schizophrenia. Methods: All English language publications from January 1989 to March 2010 as related to infection and schizophrenia were obtained. Each study selected for analysis must either deal with the direct infection of an individual and schizophrenia or maternal infection during pregnancy and the subsequent development of schizophrenia in the offspring. The primary outcome measure was the calculated odds ratio and 95% confidence interval (CI). Results: Over 300 titles and abstracts were reviewed. Eight retrospective studies regarding in utero exposure were analyzed. Five nested case-controlled studies yielded an overall odds ratio of 3.58 (95% CI: 2.71 - 4.71) with a percent attributable risk of 6.3%. Three Scandinavian populational studies yielded an overall odds ratio of 0.62 (95% CI: 0.49 - 0.79). Twenty-six papers were identified as retrospective studies focused on linking evidence of past infection in individuals with history of schizophrenia. A total of 77 microorganisms were assessed with 18 (23.4%) showing a positive association with schizophrenia. But positive associations in a given trial were negative in other trials. Conclusions: Direct infection of an individual as a cause of schizophrenia is unlikely. Results were mixed regarding maternal infection, in utero exposure, and the later development of schizophrenia in the offspring and likely accounts for a modest proportion of those with schizophrenia, possibly 6%.